Doğal Öldürücü Hücre Aktivitesinde İmmunomodulatör Etki Gösteren Moleküller

Yıl 2022, Cilt: 5 Sayı: 2, 312 - 317, 01.05.2022

Hüseyin Kaya , Seda Kuşoğlu Gültekin , Belkis Atasever Arslan

https://doi.org/10.19127/bshealthscience.1009193

Öz

Doğal Öldürücü (NK) hücreleri viral enfeksiyonlara karşı savunmadan ve malignant hücrelerin elimine edilmesinden sorumludur. NK aktivitesi, aktivatör ve inhibitör etkiye sahip yüzey reseptörleri, sitokinlerin etkisi ve diğer immun hücrelerle yaptıkları etkileşimler tarafından düzenlenir. Kanser immünoterapi stratejilerinde, T hücreleri, NK hücreler, NK-T hücreleri, B hücreleri, dendritik hücreler ve makrofajların kanser hücrelerini tanıma ve elimine etme özelliklerinden yararlanılması amaçlanır. Doğal öldürücü hücre reseptörleri, NK hücresi aktivasyonunu ve homeostazını düzenlemeden sorumludurlar. Bu reseptörlerden iletilen aktive edici ve inhibitör sinyaller arasındaki denge NK hücre işlevselliğini kontrol eder. Aktivatör reseptörler, sitotoksisite reseptörlerini (NCRs) (NKp46, NKp30 ve NKp44) ve CD94/NKG2C, NKG2D, NKG2E/H ve NKG2F reseptörlerini içerir. İnhibitör reseptörler arasında C-tipi lektin reseptörleri (CD94 / NKG2A / B) ve KIR reseptörleri (KIR-2DL ve KIR-3DL) bulunur. Derlemede NK hücrelerinin etki mekanizmaları ve NK hücre aktivitesine immunomodülatör etki gösteren moleküller ele alınmıştır .

Anahtar Kelimeler

Anti-tümör, İmmünoterapi, NK hücreleri

Molecules That Show Immunomodulator Effect on Natural Killer Cell Activity

Öz

Natural Killer (NK) cells are responsible for defending against viral infections and eliminating malignant cells. NK activity is regulated by surface receptors with activating and inhibitory effects, the action of cytokines, and their interactions with other immune cells. Cancer immunotherapy strategies aim to benefit from the ability of T cells, NK cells, NK-T cells, B cells, dendritic cells and macrophages to recognize and eliminate cancer cells. Natural killer cell receptors are responsible for regulating NK cell activation and homeostasis. The balance between activating and inhibitory signals transmitted from these receptors controls NK cell functionality. Activator receptors include cytotoxicity receptors (NCRs) (NKp46, NKp30 and NKp44) and CD94/NKG2C, NKG2D, NKG2E/H and NKG2F receptors. Inhibitory receptors include C-type lectin receptors (CD94 / NKG2A / B) and KIR receptors (KIR-2DL and KIR-3DL). In this review, the mechanisms of action of NK cells and molecules that have immunomodulatory effects on NK cell activity are discussed.

Anahtar Kelimeler

Anti-tumor, Immunotherapy, NK cells

Kaynakça

• Abel AM, Yang C, Thakar MS, Malarkannan S. 2018. Natural killer cells: Development, maturation and clinical utilization. Front Immunol, 9: 1869.
• Arslan BA, Timucin AC. 2020. Immunotherapy approaches on innate immunity for SARS-Cov-2. Acta Virol, 64(4): 389-395.
• Atasever B, Ertan NZ, Erdem-Kuruca S, Karakas Z. 2006. In vitro effects of vitamin c and selenium on nk activity of patients with β-Thalassemia major. Pediat Hematol Oncol, 23: 187–197.
• Atasever Arslan B, Erdem-Kuruca S, Karakas Z, Erman B, Ergen A. 2013. Effects of micro environmental factors on natural killer activity (NK) of Beta Thalassemia major patients. Cellular Immunol, 282: 93-99.
• Bekaroğlu MG, Arslan BA. 2014. Natural killer (NK) cells in β Thalassemia major patients. JSM Biotechnol Bioeng, 2(2): 1040.
• Berrien-Elliott MM, Romee R, Fehniger TA. 2015. Improving natural killer cell cancer immunotherapy. Curr Opin Organ Transplant, 20(6): 671-680.
• Bi J, Tian Z. 2019. NK cell dysfunction and checkpoint immunotherapy. Front Immunol, 10: 1999.
• Bowen KE, Mathew SO, Borgmann K, Ghorpade A, Mathew PA. 2018. A novel ligand on astrocytes interacts with natural cytotoxicity receptor NKp44 regulating immune response mediated by NK cells. PloS One, 13(2): e0193008.
• Castriconi R, Cantoni C, Chiesa MD, Vitale M, Marcenaro E, Conte R, Biassoni R, Bottino C, Moretta L, Moretta A. 2003. Transforming growth factor β1 inhibits expression of NKp30 and NKG2D receptors:
• Consequences for the NK-mediated killing of dendritic cells. Proc Natl Acad Sci USA, 100(7): 4120-4125.
• Cichocki F, Miller JS. 2019. Setting traps for NKG2A gives NK cell immunotherapy a fighting chance. J Clin Invest, 129(5): 1839-1841.
• Cheng M, Chen Y, Xiao W, Sun R, Tian Z. 2013. NK cell-based immunotherapy for malignant diseases. Cell Mol Immunol, 10(3): 230-252.
• Cifaldi L, Doria M, Cotugno N, Zicari S, Cancrini C, Palma P, Rossi P. 2019. DNAM-1 Activating Receptor and Its Ligands: How Do Viruses Affect the NK Cell-Mediated Immune Surveillance during the Various Phases of Infection ?. Int J Mol Sci, 20(15): 3715.
• Frutoso M, Mortier E. 2019. NK cell hyporesponsiveness: More ıs not always better. Int J Mol Sci, 20(18): 4514.
• Grudzien M, Rapak A. 2018. Effect of natural compounds on NK cell activation. J Immunol Res, 2018: 4868417.
• Gwalani LA, Orange JS. 2018. Single degranulations in NK cells can mediate target cell killing. J Immunol, 200(9): 3231-3243.
• Khan M, Arooj S, Wang H. 2020. NK cell-based immune checkpoint inhibition. Front Immunol, 11: 167.
• Kim N, Kim HS. 2018. Targeting checkpoint receptors and molecules for therapeutic modulation of natural killer cells. Frontiers in Immunol, 9: 2041.
• Konca K, Yazgan O. 2002. Yumurta tavuklarında sıcaklık stresi ve vitamin C. Hayvansal Üretim, 43(2): 16-25.
• Kumar S. 2018. Natural killer cell cytotoxicity and its regulation by inhibitory receptors. Immunol, 154(3): 383-393.
• Kwon HJ, Lee H, Choi GE, Kwon SJ, Song AY, Kim SJ, Kim HS. 2018. Ginsenoside F1 promotes cytotoxic activity of NK cells via ınsulin-like growth factor-1-dependent mechanism. Front Immunol, 9: 2785.
• Leischner C, Burkard M, Pfeiffer MM, Lauer UM, Busch C, Venturelli S. 2016. Nutritional immunology: function of natural killer cells and their modulation by resveratrol for cancer prevention and treatment. Nutr J, 15: 47.
• Lin CC, Yu CS, Yang JS, Lu CC, Chiang JH, Lin JP, Chung JG. 2012. Chrysin, a natural and biologically active flavonoid, influences a murine leukemia model in vivo through enhancing populations of T-and B-cells, and promoting macrophage phagocytosis and NK cell cytotoxicity. In Vivo, 26(4): 665-670.
• Liu H, Liu K, Huang Z, Park CM, Thimmegowda NR, Jang JH, Lee KW. 2013. A chrysin derivative suppresses skin cancer growth by inhibiting cyclin-dependent kinases. J Biol Chem, 288(36): 25924-25937.
• Long EO, Kim HS, Liu D, Peterson ME, Rajagopalan S. 2013. Controlling NK cell responses: Integration of signals for activation and inhibition. Annu Rev Immunol, 31: 227–258.
• Mahaweni NM, Ehlers FA, Bos GM, Wieten L. 2018. Tuning natural killer cell anti-multiple myeloma reactivity by targeting inhibitory signaling via KIR and NKG2A. Front Immunol, 9: 2848.
• Malaguarnera L. 2019. Influence of resveratrol on the immune response. Nutrients, 11(5): 946.
• McWilliams EM, Mele JM, Cheney C, Timmerman EA, Fiazuddin F, Strattan EJ, Awan FT. 2016. Therapeutic CD94/NKG2A blockade improves natural killer cell dysfunction in chronic lymphocytic leukemia. Oncoimmunol, 5(10): e1226720.
• Meza-Guzman LG, Keating N, Nicholson SE. 2020. Natural killer cells: Tumor surveillance and signaling. Cancers (Basel), 12(4): 952.
• Miller JS. 2001. The biology of natural killer cells in cancer, infection, and pregnancy. Experiment Hematol, 29(10): 1157-1168.
• Narni-Mancinelli E, Chaix J, Fenis A, Kerdiles YM, Yessaad N, Reynders A, Gregoire C, Luche H, Ugolini S, Tomasello E, Walzer T, Vivier E. 2011. Fate mapping analysis of lymphoid cells expressing the NKp46 cell surface receptor. Proc Natl Acad Sci USA, 8(45): 18324-18329.
• Nayyar G, Chu Y, Cairo MS. 2019. Overcoming resistance to natural killer cell based ımmunotherapies for solid tumors. Front Oncol, 9: 51.
• Netter P, Anft M, Watzl C. 2017. Termination of the activating NK cell immunological synapse is an active and regulated process. J Immunol, 199(7): 2528-2535.
• Orr MT, Lanier LL. 2010. Natural killer cell education and tolerance. Cell, 142(6): 847-856.
• Pallmer K, Barnstorf I, Baumann NS, Borsa M, Jonjic S, Oxenius A. 2019. NK cells negatively regulate CD8 T cells via natural cytotoxicity receptor (NCR) 1 during LCMV infection. PloS Pathog, 15(4): e1007725.
• Pan P, Huang YW, Oshima K, Yearsley M, Zhang J, Arnold M, Wang LS. 2019. The immunomodulatory potential of natural compounds in tumor-bearing mice and humans. Critical Rev Food Sci Nutri, 59(6): 992-1007.
• Paul S, Lal G. 2017. The Molecular mechanism of natural killer cells function and ıts ımportance in cancer ımmunotherapy. Front Immunol, 8: 1124.
• Pazina T, Shemesh A, Brusilovsky M, Porgador A, Campbell KS. 2017. Regulation of the functions of natural cytotoxicity receptors by interactions with diverse ligands and alterations in splice variant expression. Front Immunol, 8: 369.
• Purdy AK, Campbell KS. 2009. Natural killer cells and cancer: regulation by the killer cell Ig-like receptors (KIR). Cancer Biol Ther, 8(23): 13-22.
• Sarhan D, Cichocki F, Zhang B, Yingst A, Spellman SR, Cooley S, Miller JS. 2016. Adaptive NK cells with low TIGIT expression are inherently resistant to myeloid-derived suppressor cells. Cancer Res, 76(19): 5696-5706.
• Shifrin N, Raulet DH, Ardolino, M. 2014. NK cell self tolerance, responsiveness and missing self recognition. Semin Immunol, 26(2): 138-144.
• Siewiera J, Gouilly J, Hocine HR, Cartron G, Levy C, Al-Daccak R, Jabrane-Ferrat N. 2015. Natural cytotoxicity receptor splice variants orchestrate the distinct functions of human natural killer cell subtypes. Nat Commun, 6: 10183.
• Silva-Santos B, Strid J. 2018. Working in NK mode: natural killer group 2 member d and natural cytotoxicity receptors in stress-surveillance by γδ T cells. Front Immunol, 9: 851.
• Sun C, Sun H. 2019. The rise of NK cell checkpoint inhibitors as promising therapeutic targets in cancer immunotherapy. Front Immunol, 10: 2354.
• Vitale M, Sivori S, Pende D, Augugliaro R, Di Donato C, Amoroso A, Malnati M, Bottino C, Moretta L, Moretta A. 1996. Physical and functional independency of p70 and p58 natural killer (NK) cell receptors for HLA class I: their role in the definition of different groups of alloreactive NK cell clones. Proc Natl Acad Sci USA, 93(4):1453-1457.
• Yin X, Liu T, Wang Z, Ma M, Lei J, Zhang Z, Han X. 2018. Expression of the inhibitory receptor TIGIT is up-regulated specifically on NK cells with CD226 activating receptor from HIV-infected individuals. Front Immunol, 9: 2341.
• Wang Y, Lu J, Jiang B, Guo J. 2020. The roles of curcumin in regulating the tumor immunosuppressive microenvironment. Oncol Lett, 19(4): 3059-3070.